EN   EN 
 
 
 EUROPEAN  
COMMISSION   
Brussels, 17.12.2021  
COM(2021) 998 final  
2021/0432 (COD)  
 
Proposal for a  
REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL  
amending Regulation (EU) No 536/2014 as regards a derogation from certain obligations 
concerning investigational medicinal products made available in the United Kingdom 
with respect to Northern Ireland as well as in Cyprus, Ireland and Malta  
(Text with EEA relevance)   EN 1  EN EXPLANATORY MEMORANDUM  
1. CONTEXT  OF THE  PROPOSAL  
• Reasons for and objectives of the proposal  
Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”)  of the 
Agreement on the withdrawal of the United Kingdom of Great Britain and Northern 
Ireland from the European Union and the European Atomic Energy Community1 (the 
‘Withdrawal Agreement’) , the importation  of investigational medicinal products 
from third countries  into the Union or Northern Ireland is subject to the possession of 
a manufacturing and import authorisation.  These shall be in compliance with the 
obligations of the EU acquis for clinical trials . 
During these last years, the U nited Kingdom in respect of Northern Ireland  as well as 
the small markets of the European Union (i.e . Malta, Ireland and Cyprus) that are 
dependent on supply of medicinal products from the United Kingdom, have raised 
issues with respect to the ability of economic operators to comply with all provisions 
of the acquis for medicines  after the end of the transition period provided for in 
the Withdrawal Agreement , including medicines  used in clinical trials , having  
regard in partic ular to the importation requirements .  
The Commission Notice of 25 January 20212 provides for a grace period of one year 
(until end -December 2021) , including for the importation requirements  for 
investigational medicines , to ensure undisrupte d supply of medicines to Northern 
Ireland, Cyprus, Ireland and Malta .  
Despite the transition period, it still prove s very difficult for certain  operators 
currently based in parts of the United Kingdom other than Northern Ireland  to adapt 
as required by the Protocol.  The main reasons are the too high adjustment costs 
relative to the small size of the N orthern Irish market and the complex logistics 
involved, for which no viable alternative logistical hubs in Northern Ireland ha ve 
been identified.   
For the markets of Cyp rus, Malta and Ireland, the same issues arose, and in addition,  
difficulties were seen with to ensure that clinical trial participants have access to 
certain medicinal products due to supply chains reliance on other parts of the United 
Kingdom than Northern Ireland .  
Disruption in supply of investigational medicinal products would pose potential risk 
to the safety and well -being of participants in ongoing clinical trials as well as hinder 
the setting up of new clinical trials in these Member States a nd in Northern Ireland.  
The objectives of this proposal are to address the issues related to investigational 
medicinal products,  to prevent an adverse impact on the ir supply and , as a result,  on 
the execution of clinical trials authorised under Regulation  (EU) 536/20143 in 
Northern Ireland, Cyprus, Ireland and Malta . 
                                                 
1 OJ L 29, 31.1.2020, p. 7.  
2 Commission Notice of 25 January 2021 on the application of the Union’s pharmaceutical acquis  in 
markets historically dependent on medicines supply from or through Great Britain after the end of the 
transition period,  (OJ C 27, 25.1.2021, p. 11 ).  
3 Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on 
clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (OJ L 158, 
27.5.2014, p. 1) .  EN 2  EN This pro posal allows exceptionally that the manufacturing and import authorisation 
is not required for investigational medicinal products imported  into Cyprus, Ireland, 
Malta and Northern Ireland  from parts of the United Kingdom other than Northern 
Ireland, provided that certain conditions are fulfilled . For Cyprus, Ireland and Malta, 
this derogation is of a temporary nature as it is expected that these markets will 
gradually be supplied through Member States. A transition period of 3 years seems 
sufficient.  
Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was 
made dependent  on the full functionality of the European Portal and Database. The 
Commission published th e notice of full functionality  on 31 July 2021 , triggering a 
6-month period before applicability on 31 January 2022.4 As a transit ional measure, 
during the first year (until 31  January 2023), spon sors can chose to s ubmit a clinical 
trial application  in line with the rules of Regulation (EU) 536/2014  or through the 
rules of Directive 2001/20 /EC5. Trials authorised under that Directive  can continue 
until 31 January 2025.  
Therefore, this proposal should be read in conjunction with the conceptual ly identical 
change s to Directive 2001/20  proposed in COM(2021 )997 of 17 December 2021  as 
both legal act s can apply to different clinical trials in the EU until 31 January 2025.  
For this reason, this separate proposal  was given an exemption from an additional 
fiche for the agenda planning. Considering the urgency needed to address the issues, 
the roadmap for this initiative will not be provided.  
• Consistency with existing policy provisions in the  policy area  
A comprehensive Union medicinal products legislative framework was established, 
in particular Directive 2001/83/EC6, Directive 2001/20/EC  and Regulation (EU) No 
536/2014 , which are of relevance for this initiative that will complement and amend 
them.  
This proposal is consistent with the objective to protect participants of clinical trials 
and public health in the small markets of the Union and in Northern Ireland.  
• Consistency with other Union policies  
This proposal does not affect other Union policie s, except for the health and internal 
market rules . As a consequence , the assessment of the consistency with other Union 
policies is not considered necessary.  
2. LEGAL  BASIS,  SUBSIDIARITY  AND  PROPORTIONALITY  
• Legal  basis  
As th is proposal  amends Regulation  (EU) No 536/2014 , the same lega l basis   
Article s 114 and 168(4)(c)  TFEU   are considered the appropriate legal basis  for this 
proposal as well . 
                                                 
4 Commission Notice of 25 January 2021 on the application of the Union’s pharmaceutical acquis  in 
markets historically dependent on medicines supply from or through Great Britain after the end of the 
trans ition period,  (OJ C 27, 25.1.2021, p. 11 ). 
5 Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the 
approximation of the laws, regulations and administrative provisions of the Member States relating to 
the implementation of good clinical practice in the conduct of clinical trials on medicinal products for 
human use (OJ L 121, 1.5.2001, p. 34).  
6 Directive 2001/83/EC of t he European Parliament and of the Council of 6 November 2001 on the 
Community code relating to medicinal products for human use (OJ L 311, 28.11.2001, p. 67).  EN 3  EN • Subsidiarity  (for non-exclusive  competence)   
This proposal provides exemptions from  the provisions  of the EU pharmaceutical 
legislation and can only be achieved by an amendment of the basic act at EU level.  
This proposal aims to provide derogations for medicinal products distributed to 
Northern Ireland, Cyprus, Ireland and Malta  that are  used as investigational 
medicinal products in clinical trials  in those countries . 
• Proportionality  
The proposal covers the exemption from  the importation requirements for 
investigational medicin al products  to ensure  their continu ed supply and avoid delays 
or interruptions to the setting up and conduct of clinical trials in the Union  and in 
Northern Ireland . 
The proposal is restricted to investigational medicines made  exclusively  available  in 
Northern Ireland and the small markets of th ose EU Member States   Cyprus, Malta 
and Ireland   that are dependent o n the UK market.  
• Choice  of the instrument  
As the initiative amends Regulation (EU) No 536/2014 , a proposal for a Regulation 
of the European Parliament and Council is considered the appropriate instrument.  
3. RESULTS  OF EX-POST  EVALUATIONS,  STAKEHOLDER  
CONSULTATIONS  AND  IMPACT  ASSESSMENTS  
• Ex-post evaluations/fitness  checks  of existing  legislation  
Not applicable  
• Stakeholder  consultations  
This initiative is proposed following bilateral discussion with the con cerned national 
authorities and industry  associations , who have expressed strong concern s due to the 
risk of interruptions of ongoing or future clinical trials due to the requirements for 
importation  of investigational medicinal products . 
Considering that targeted consultations with the Member States concerned and the 
stakeholders took place, another open public consultation will not be carried out.  
• Impact  assessment  
The proposal is exempted from the impact assessment due to the urgency of the 
situation , to ensure public health through  the continued supply of investigation 
medicinal products  for clinical trials  in Northern Ireland and the small markets of the 
EU Member States that are depend ent on the United Kingdom  for their supplies . 
• Regulatory  fitness  and simplification  
By waiving certain regulatory requirements  for the importation of investigational 
medicinal products , provided certain conditions are fulfilled , the proposal reduces  
compliance costs in particular as regards SMEs .  
• Fundamental  rights  
The proposed Regulation contributes to achieving a high level of human health 
protection as set out in Article 35 of the EU Charter of Fundamental Rights.  EN 4  EN 4. BUDGETARY  IMPLICATIONS  
No budgetary implications are foreseen.  
5. OTHER  ELEMENTS  
• Implementatio n plans  and monitoring,  evaluation  and reporting  arrangements  
The initiative applies to the United Kingdom  in respect of N orthern Ireland  that must 
implement it and notify to the Commission the implementation planning associated 
with this initiative. The Member States concerned as well must take the necessary 
measures to implement the initiative. The Commission will further monitor its 
implementation.   
• Detailed  explanation  of the specific  provisions  of the proposal  
Not applicable for this proposal.  EN 5  EN 2021/0432 (COD)  
Proposal for a  
REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL  
amending Regulation (EU) No 536/2014 as regards a derogation from certain obligations 
concerning investigational medicinal products made available in the United Kingdom 
with respect to Northern Ireland as well as in Cyprus, Ireland and Malta  
(Text with EEA relevance)  
THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,  
Having regard to the T reaty on the Functioning of the European U nion, and in particular 
Articles  114 and 168(4) , point (c), thereof,  
Having regard to the proposal from the European Commission,  
After transmission of the draft legislative act to the national parliaments,  
Having r egard to the opinion of the European Economic and Social Committee1,  
Having regard to the opinion of the Committee of the Regions2,  
Acting in accordance with the ordinary legislative procedure,  
Whereas:  
(1) The Agreement on the withdrawal of the United Kingdom of Great Britain and 
Northern Ireland from the European Union and the European Atomic Energy 
Community3 (the ‘Withdrawal Agreement’) was concluded on behalf of the Union by 
Council Decision (EU) 2020/135  4 and entered into force on 1 February 2020. The 
transition period referred to in Article 126 of the Withdrawal Agreement, during which 
Union law continue d to apply to and in the United Kingdom in accordance with 
Article 127 of the Withdrawal Agreement (the ‘transition period’), end ed on 31 
December 2020.  On 25 January 2021, the Commission issued a Notice5 (‘the Notice’)  
on the application of the Union’s pha rmaceutical acquis in markets historically 
dependent on medicines supply from or through Great Britain (i.e. Cyprus, Ireland, 
Malta and Northern Ireland) after the end of the transition period . This Notice includes 
explanations of how the Commission would apply the Union’s pharmaceutical acquis 
in those markets with regard to investigational medicinal products.  The Notice is to 
cease to be applied  on 31 December 2021.  
                                                 
1 OJ C , , p. .  
2 OJ C , , p. .  
3 OJ L 29, 31.1.2020, p. 7.  
4 Council Decision (EU) 2020/135 of 3 0 January 2020 on the conclusion of the Agreement on the 
withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and 
the European Atomic Energy Community (OJ L 29, 31.1.2020, p. 1 ). 
5 Commission Notice  – Application of the Union’s pharmaceutical acquis in markets historically 
dependent on medicines supply from or through Great Britain after the end of the transition period  
(2021/C 27/08 )(OJ C 27, 25.1.2021, p. 11 ). EN 6  EN (2) In accordance with  the Protocol on Ireland/Northern Ireland , which forms an integral 
part of the Withdrawal Agreement, investigational medicinal products used in clinical 
trials  in Northern Ireland are to comply with Union law . 
(3) Regulation (EU) No 536/2014 of the European Parliament and of the Council6 lays 
down the rules for investigat ional medicinal products intended to be used in clinical 
trials in the U nion. That Regulation applies from 31 January 2022.  
(4) In accordance with  Article 61(1) of Regulation (EU) No 536/2014 , read in conjunction 
with the Protocol on Ireland/Northern Ireland , the import  of investigational medicinal 
products from third countries  into the Union or Northern Ireland is subject to the 
holding of a manufacturing and import authorisation.  Cyprus, Ireland, Malta and 
Northern Ireland have historically relied on  supply of medicinal products, including 
investigational medicinal products, from or through parts of the United Kingdom other 
than Northern Ireland, and the supply chains for these markets have not yet been fully 
adapted to comply with Union law  In order to ensure that clinical trial participants in 
Cyprus, Ireland, Malta and Northern Ireland  continue to have access to  new, 
innovative or improved treatments , it is necessary to amend Regulation (EU) No 
536/2014  to provide for a derogation from the requireme nt of the holding of a 
manufacturing and import authorisation for investigational medicinal products 
imported  into those markets  from parts of the United Kingdom other than Northern 
Ireland . However, both in order to ensure  the quality of those investigational medicinal 
products and  to avoid compromising the integrity of the internal market , certain 
conditions should be laid down .  
(5) Regulation (EU) No 536/ 2014 should therefore be amended accordingly . 
(6) In light of the requirement of uniform application of Union law in the Member States, 
the derogations applicable in Cyprus, Ireland and Malta should be of a temporary 
nature  only.  
(7) In order  to ensure legal continuity for operators active in this sector  and to guarantee 
the continuous access of participants in clinical trials  in Cyprus, Malta, Ireland and 
Northern Ireland to investigational medicinal products  from the date of application of 
Regulation (EU) No 536/2014 , this Regulation  should enter into force as a matter of 
urgency and apply retroactively from the da te at which Regulation (EU) 536/2014  
becomes applicable ,  
HAVE ADOPTED THIS REGULATION:  
Article 1  
In Article 61(1) of Regulation 536/2014, the following subparagraph is added:  
“However , the import of investigational medicinal products from other parts of the United 
Kingdom into Northern Ireland and, until 31 December 2024, into Cyprus, Ireland and Malta 
shall not be subject to the holding of a  manufacturing and import authorisation , provided that 
the following conditions are fulfilled:  
(a) the investigational medicinal products have undergone certification of batch release  
either in the Union or in parts of the United Kingdom other than Northern Ireland to 
verify compliance with the requireme nts set out in Article 63 (1);  
                                                 
6 Regulation (EU) No 536/2014 of the European Parliam ent and of the Council of 16 April 2014 on 
clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (OJ L 158, 
27.5.2014, p. 1 ). EN 7  EN (b) the investigational medicinal products  are only made available to clinical trial 
participant s in the Member State into  which the investigational medicinal products  
are imported or, if imported into Northern Ireland , are only made available to clinical 
trial participants in Northern Ireland .” 
Article 2 
This Regulatio n shall enter into force on the  day following that of its publication in the 
Official Journal of the European Union . 
It shall apply from 31 January 2022.  
This Regulation shall be binding in its entirety and directly applicable in all Member States.  
Done at Brussels,  
For the European Parliament  For the Council  
The President  The President